Overlapping and distinct functions provided by fgf17, a new zebrafish member of the Fgf8/17/18 subgroup of Fgfs

Members of the fibroblast growth factor (Fgf) family are important signalin g molecules in several inductive and patterning processes, and act as brain organizer-derived signals during formation of the early vertebrate nervous system. We isolated a new member of the Fgf8/17/18 subgroup of Fgfs from t he zebrafish, and studied its expression and function during somitogenesis, optic stalk and midbrain-hindbrain boundary (MHB) development. In spite of a slightly higher aminoacid similarity to Fgfs, expression analysis and ma pping to a chromosome stretch that is syntenic with mammalian chromosomes s hows that this gene is orthologous to mammalian Fgf17. These data provide a further example of conserved chromosomal organization between zebrafish an d mammalian genomes. Using an mRNA injection assay, we show that fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally express ed. Direct comparison of the expression patterns of fgf17 and fgf8 suggest however a possible cooperation of these Fgfs at later stages in several tis sues requiring Fgf signaling. Analysis of zebrafish MHB mutants demonstrate s a gene-dosage dependent requirement of fgf17 expression for the no isthmu s/1 pax2.1 gene, showing that no isthmus/pax2.1 functions upstream of fgf17 at the MHB in a haplo-insufficient manner, similar to what has been report ed for mammalian pax2 mutants. In contrast, only maintenance of fgf17 expre ssion is disturbed at the MHB of acerebellar/fgf8 mutants. Consistent with a requirement for fgf8 function, implantation of FGF8-soaked beads induces fgf17 expression, and expression is upregulated in aussicht mutants, which display upregulation of the Fgf8 signaling pathway. Taken together, our res ults argue that Fgf8 and Fgf17 act as hierarchically organized signaling mo lecules during development of the MHB organizer and possibly other organize rs in the developing nervous system. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.